Ocular surface diseases, especially ocular infections, encompass a plethora of pathologies with overlapping conditions leading to common sequels: dysfunction of the ocular tear film and/or the integrity of the ocular surface. The ocular surface is richly innervated by sensory nerves, therefore, any stimulus that affects these tissues can lead to a variety of symptoms. These range from mild discomfort to grittiness, foreign body sensation, irritation, and dryness affecting the quality of life of millions. Furthermore inflammation can cause damage to the various structures of the ocular surface: i.e. scarring of tissues underlying the conjunctival epithelium and destruction of the Becher-cells leading to dry eyes and/or causing irregularity of the corneal surface that might result in glare. In severe cases, where the condition is chronic with surface damage, it might lead to mild to profound decreases in vision as seen in severe dry eyes syndromes, vernal keratoconjunctivitis or infectious diseases as trachoma.
Specifically, trachoma is one of the neglected tropical diseases and remains the world's leading infectious cause of blindness. It is estimated that more than 500 million people are at high risk of infection, over 140 million are infected. It affects clinically about 21.4 million people of whom about 2.2 million are visually impaired and 1.2 million are blind. It is responsible, at present, for more than 3% of the world's blindness but the number keeps changing due to the effect of socio-economic development and current control programmes for this disease.
Chlamydia trachomatis also causes morbidity worldwide through infections manifesting in the genitourinary tract causing cervicitis and/or urethritis. In fact these infections are the most common form of bacterial sexually transmitted diseases (STDs), placing enormous socioeconomic burden on societies (Blake et al, Sex. Transm. Dis., 2004, 31(2), 85-95). Chlamydia pneumoniae (now classified as Chlamydophila pneumoniae) was first associated with mild respiratory infections but has recently emerged as a relevant pathogen associated with atherosclerosis, adult-onset asthma, macular degeneration and certain other chronic diseases (Watson et al, Clin. Sci., 2008, 114(8), 509-31; Shen et al, Br. J. Ophthalmol., 2009, 93(3), 405-8). The zoonotic Chlamydophila psittaci constitutes an occupational hazard for workers in the poultry and farming industry, and persons exposed to infected avian species (Vanrompay et al, Emerg. Infect. Dis., 2007, 1108-10).
Although affecting the majority of individuals with ocular symptoms, ocular surface diseases, especially ocular surface infections, are globally under-recognized and neglected. This is also reflected in drug development as most of the topical drugs used in the management of ocular surface diseases are optimized for intraocular delivery meaning that they are not developed to reach the ocular surface but to overcome it in its barrier function. Drug penetration into the anterior chamber is improved by increasing lipophilicity for better transcellular transport and by the use of enhancers like actin filament inhibitors, surfactants, and bile salts to open tight junctions for better paracellular absorption through the ocular surface. The use of these drugs contributes inevitably on the long run to more ocular surface dysfunction. Similar findings are also seen in chronic usage of topical therapeutics prescribed for other ocular conditions as glaucoma where the prevalence of ocular surface disease in patients with glaucoma is fairly common. Leung et al. reported that half of their patients being treated for glaucoma had ocular surface disease at least in one eye seeing as exacerbation of underlying ocular surface disease secondary to medications (Leung E W et al., J. Glaucoma. 2008 August; 17(5):350-5. doi: 10.1097/IJG.0b013e31815c5f4f.). On the other hand, anti-inflammatory therapy of the ocular surface often leads to adverse events in the intraocular compartment, too. Secondary glaucoma and cataract formation are common in chronic topical steroid usages.
The conjunctiva and its underlying structures are now accepted as a part of the mucosa-associated lymphoid tissue (MALT) and are annotated as the conjunctiva-associated lymphoid tissue (CALT) or the eye-associated lymphoid tissue (EALT; Nelson D. et al., The conjunctiva: anatomy and physiology. In Cornea (3rd edition, vol 1, eds.: Krachmer J H, Mannis M J, Holland E J) 2010: 25-32, Mosby, Elsevier).
CALT has the typical components of a physiologically protective mucosal immune system, as it contains diffuse lymphoid tissues and lymphoid follicles that form the efferent and the afferent limbs, respectively, of a lymphoid tissue. Thus, CALT can detect antigens from the ocular surface, present them to lymphoid cells and generate protective effector cells; together, these properties signify the presence of a mucosal immune system at the conjunctiva (Knop E. and Knop N., J. Anat., 2005, 206, 271-285; Chandler J W et al., Ophtalmology, 1983, 90, 585-591). The delivery of vaccines via the conjunctiva would also be an attractive option for mucosal immunization, as eye drops are easily administered, drop-count dosing is feasible, conjunctival inflammation is easily noticeable and, as the conjunctiva is interconnected with the nasal mucosa via the tear ducts, administration of antigens to the conjunctival sac would also drain to reach the nasal-associated lymphoid tissue (NALT). Conjunctival immunization with live attenuated vaccines has been used in veterinary applications and proven an efficient route in many animal models for different infectious diseases (Lim M., et al., Br. J. OPhtalmol., 2006, 90, 1468-1471; Okada K. et al., Adv. Otorhinolaryngol., 2011, 72, 72-31), for example in poultry against Newcastle virus, infectious bursitis virus, chicken herpes virus and turkey herpes virus, in feline viral rhinotracheitis, calicivirus and panleukopeas, and in goats and sheep against Brucella ovis (Steven P, Gebert A, Ophthalmic Res., 2009, 42(1), 2-8; Kageyama M. et al., Arch. Histol. Cytol., 2006, 69(5), 311-22).
Barisani-Asenbauer T. et al. (Acta Ophthalmologica, 2012, 90, Issue Suppl. s249, 2844) describe studies, wherein animals are immunized with tetanus toxoid together with inactivated Bordetella pertussis. 
Ariful Islam M. et al. (Int. J. Nanomed., 2012, 7, 6077-6093) disclose chitosan microspheres for oral or nasal administration of vaccines.
The use of Brucella ovis glycoproteins encapsulated in mannosylated nanoparticles of 300 nm size is disclosed by Costa Martins R. et al (J. Controlled Disease, 2012, 162, 553-560).
Walcher P. et al. (Vaccine, 2008, 26, 6832-6838) describe the use of bacterial ghosts for expressing ZP2 polypeptides and their use as fertility control in opossums as facial sprays randomly reaching the nasal and eye area.
Eko F. O. et al. (Human Vaccines, 2008, 4:3, 176-183) also disclose the use of a bacterial ghost vaccine containing Chlamydia antigens for the treatment of Chlamydia trachomatis. 
Abbas, M. (Expert Rev. Vaccines, 2012, 97-116), describes a potential vaccine system using bacterial ghost expressing antigens.
In Kudela P. et al. (J. Biotechnol., 2011, 153, 167-175) bacterial ghosts as antigen and drug delivery system without the use of further adjuvants for ocular surface diseases is described and did not show a cytotoxic effect in the studies. To date, the number of mucosal registered vaccines for human application remains very limited and is principally based on live attenuated pathogens and/or vectors, which contain their own danger signals and mechanisms of mucosal entry (Perrie Y., et al., Int. J. Pharm., 2008, 8, 364(2), 272-80). It is further hampered due to the lack of sufficient overall immune response which provides effective vaccination.
Thus there is still an unmet demand for vaccines which are not only a safe and efficient alternative to live attenuated vaccines but also provide protection at the site of primary infection—the mucosal tissues especially the ocular surface. The development of treatment options targeting the ocular surface would be helpful to reach protection locally and/or reduce the rate of severity of sequels. Optimally a delivery platform is needed that penetrates ocular surface cells with properties that hinders the trans- and paracellular transport into the normal eye on one side (Gukasyan H J et al., Biotechnology: Pharmaceutical Aspects Volume VII, 2008, pp 307-320) and on the other side is safer than live attenuated vaccines.